Ervin CM, Fehnel S, Carson R, Kurtz C, Shiff S, Johnston J. Selecting chronic constipation (CC) clinical trial endpoints: incorporating the patient's voice. Poster presented at the 2010 ISPOR 15th Annual International Meeting; May 28, 2010. [abstract] Value Health. 2010 May; 13(3):A74.

OBJECTIVES: 1. Identify a comprehensive set of symptoms for measurement in CC clinical trials. 2. Achieve saturation and provide support for the content validity of the corresponding set of endpoints in accordance with FDA’s PRO guidance.

METHODS: Twenty-eight in-depth interviews were conducted in two phases, in different geographic locations, with participants meeting modified Rome II criteria for CC. A semi-structured interview guide was used, beginning with a series of open-ended questions to elicit all relevant symptoms, followed by interviewer probes to fully understand the relationships among the concepts. Multiple rating and ranking methods were used to develop a subset of CC symptoms of greatest importance to patients. For example, participants were asked to identify their most bothersome CC symptoms, as well as those in which they would most like to see an improvement with treatment.

RESULTS: When asked to describe their CC symptoms, the patients reported 62 potentially distinct concepts: 12 bowel symptoms, 21 abdominal symptoms, 25 additional physical symptoms, and 4 mental or emotional issues. Patient descriptions of symptoms revealed that symptom terms were highly related and/or could be considered secondary to CC. Results of the subsequent rating and ranking tasks suggest that the concepts of stool frequency, stool consistency, straining, incomplete evacuation, abdominal pain, abdominal discomfort, and bloating were distinct and comprise patients’ most bothersome symptoms. Further, improvements in these symptoms would constitute an improvement in patients’ CC overall, and PRO items addressing these symptoms were found to be clear and comprehensive.

CONCLUSIONS: Patient input is vital to identify the full spectrum of symptoms, and to determine an optimal set of clinical trial endpoints. Interview results suggest that a variety of techniques may be necessary to demonstrate concept saturation and identify those symptoms which accurately represent a functional disorder such as CC.